IL-6 and sIL-6R increase cartilage matrix proteins expression in chondrocyte

Objective: Elevated concentrations of interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6Ra) in the synovial fluid of the temporomandibular joint (TMJ) have been implicated in the joint cartilage destruction associated with TMJ disorders. We demonstrated that IL-1b promotes the resolution system of cartilage matrix turnover through an increase in inflammatory cytokine production by chondrocytes and that it also may promote the autocrine action of IL-6 through an increase in IL-6R expression in chondrocytes (Life Sci 79, 764-771, 2006). In this study, we examined the effect of IL-6 and sIL-6Ra on cell growth and alkaline phosphatase (ALPase) activity. We also examined the expression of Sox-9, cartilage matrix proteins, bone morphogenetic protein (BMP)-7, and BMP receptors (BMPR) in chondrocytes. Methods: The cells were cultured with or without 50 ng/mL IL-6 and/or 30 ng/mL sIL-6Ra for up to 28 days. The levels of mRNA expression for Sox-9, the cartilage matrix proteins, BMP-7, and BMPR were determined using real-time PCR; protein levels were determined using ELISA. The proteoglycans were stained with Alcian blue. Results: Cell proliferation increased slightly in the presence of both IL-6 and sIL-6Ra after 7 days of culture. ALPase activity, a marker enzyme used to differentiate chondrocytes, decreased markedly in the presence of both IL-6 and sIL-6Ra after 10 days. The expression of Sox-9, aggrecan core, and Alcian blue-positive proteoglycans did not change with IL-6 and sIL-6Ra, whereas the expression of type II collagen, link protein, BMP-7, and BMPR increased in the presence of both IL-6 and sIL-6Ra after 7 days. Conclusion: These results suggest that IL-6 in the presence of sIL-6Ra suppresses the differentiation of chondrocytes and induces the repair of arthrodial cartilage through an increased in the expression of cartilage matrix proteins by autocrine action of BMP-7 in the cells.